Seasonality has a major effect on the spatiotemporal dynamics of natural systems and their populations and is the driving force behind the transmission of influenza in temperate regions. Although the seasonality of influenza in temperate countries is widely recognized, inter-regional spread of influenza in the United States have not been well characterized. This research will study the seasonality of influenza throughout the United States by using weekly pneumonia and influenza (P&I) mortality to model inter-region and inter-city movement of seasonal influenza in the United States between 1968 and 2007. This project aims to identify the underlying wave of seasonal influenza spread in the United States and the dependence of the timing and spread of influenza on the dominant circulating influenza type or subtype in a given influenza season. This goal will be achieved by accomplishing the following aims: 1) identifying the spatial and temporal patterns of seasonal influenza in the U.S. from 1968 to 2007, 2) comparing the spatial and temporal patterns of seasonal influenza in the U.S. by dominant type or subtype of influenza, 3) identifying source locations of influenza transmission in the U.S., 4) and determining the dominant spreading process of seasonal influenza in the U.S. Average time to death from P&I will be used to determine the epidemic timing and direction of wave progression for each influenza season. It will also be used to identify seed locations for influenza transmission and assess the velocity of wave progression. Ordinary least squares will be used in order to develop linear trend surfaces for each influenza season and to depict the main trend in the spatial progression of each influenza season. Spatial autocorrelation will be used to detect the dominant spreading process of seasonal influenza in the U.S. (e.g. contagious, hierarchical, or mixed process). In addition, the average time seasonal influenza takes to spread across the United States and the average time between regional peak and national peak by dominant influenza subtype and season will be determined. Identifying spatiotemporal patterns could improve epidemic prediction and prevention. This research will determine the spatial and temporal characteristics of seasonal influenza in the U.S. and show if these characteristics differ by dominant influenza sub-type. Accomplishing this research will greatly aid public health professionals in refining influenza intervention strategies that include better placement and distribution of vaccines and other medicines. PUBLIC HEALTH RELEVANCE: The completion of the proposed research has broad application for the planning of intervention strategies for pandemic and epidemic influenza in the U.S. Knowledge of the timing and spatial spread of influenza could severely limit the morbidity and mortality associated with epidemic influenza, as well as with a future pandemic. The knowledge gained as a result of this dissertation will allow public health officials to refine currnt influenza intervention strategies in order to more effectively and efficiently utilize influenza interventions.